Background: Although congenital anomalies are established risk factors for developing childhood cancer, less is known about health outcomes among survivors of childhood cancer with known congenital anomalies. Therefore, we estimated the risk of chronic health conditions (CHCs) and subsequent malignant neoplasms (SMNs) among survivors of childhood cancer by congenital anomaly status in the Childhood Cancer Survivor Study (CCSS). Methods: Overall, 22,247 five-year survivors self-reported congenital anomalies. We included 16 conditions present at birth, excluding self-reported genetic conditions. Patient-reported CHCs were graded using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03). Self-reported SMNs were confirmed through pathology report review. Hazard ratios (HR) of CHCs comparing survivors with vs. without congenital anomalies and their 95% confidence intervals (CI) were estimated using Cox regression with age as the time scale, adjusted for race/ethnicity, education, household income, health insurance, and original cancer treatment. Results: Among survivors (median age at cancer diagnosis 6 years (range 3-12), age at follow-up 31 years (range 25-39)), 16.9% (n = 3880) reported a congenital anomaly. The most common anomalies included: large/multiple birth marks (n = 1540, 40.4%); congenital heart defects (n = 693, 18.4%); and kidney, bladder, or genital abnormalities (n = 607, 14.6%). Relative to survivors without anomalies, those with anomalies more commonly had astrocytoma, Wilms tumor, and neuroblastoma primary cancers (p < 0.001), treated with radiation (p = 0.011), cyclophosphamide (p < 0.001), anthracyclines (p < 0.001), and epipodophyllotoxins (p = 0.044), and younger age at cancer diagnosis (11.3% vs. 5.7% diagnosed prior to one year of age, p < 0.001). Survivors with anomalies were more likely to develop any CHC (CTCAE grades 1-5 HR: 1.31, 95% CI: 1.23, 1.39); severe, disabling, life-threatening or fatal CHCs (grades 3-5 HR: 1.42 (95% CI: 1.28, 1.58); and multiple CHCs (≥2 conditions HR: 1.36, 95% CI: 1.27, 1.46; ≥3 conditions HR: 1.49, 95% CI: 1.37, 1.63). Survivors with anomalies had increased risk for adverse outcomes across multiple systems (all p < 0.001), including: hearing/vision/speech (HR: 1.37); urinary (HR: 1.42); hormonal/endocrine (HR: 1.24); heart/circulatory (HR: 1.35); digestive (HR: 1.49); and brain systems (HR: 1.42). We observed no differences in the risk of any SMN by congenital anomaly status (HR: 1.12, 95% CI: 0.90, 1.38). Conclusions: In our assessment, survivors of childhood cancer with self-reported congenital anomalies had an increased risk of developing CHCs compared to survivors without reported anomalies, but no increased risk of SMNs. Evaluating congenital anomalies allows identification of a population of childhood cancer survivors at high risk for poor long-term health outcomes.